Itraconazole and domperidone: a placebo-controlled drug interaction study

Yoshizato, Tsuneaki; Kotegawa, Tsutomu; Imai, Hiromitsu; Tsutsumi, Kimiko; Imanaga, Junko; Ohyama, Tetsuji; Ohashi, Kyoichi

doi:10.1007/s00228-012-1258-x

Cited by 17 publications

(13 citation statements)

References 33 publications

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“…Itraconazole is a potent inhibitor of CYP3A. Five repeated administrations of 200 mg of itraconazole have been shown to increase the plasma exposure of domperidone by 3.2‐fold . Four repeated administrations of 200 mg of itraconazole increased the plasma exposure of atorvastatin acid, atorvastatin lactone, and felodipine about 3‐, 4‐, and 6‐fold, respectively .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole

Liu

Zhang

Chen

et al. 2017

The Journal of Clinical Pharma

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Apatinib is a small-molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with advanced-stage gastric cancer or gastroesophageal junction cancer who have progressed or recurred after at least 2 kinds of systemic chemotherapy. In vitro data indicate that cytochrome P450 (CYP) 3A4 is the primary CYP isoenzyme involved in the metabolism of apatinib. Pharmacokinetic drug-drug interactions of apatinib and (1) a CYP3A4 inducer (rifampin) or (2) a CYP3A inhibitor (itraconazole) were clinically evaluated in healthy volunteers. Compared with the single administration of apatinib, its coadministration with rifampin resulted in a 5.6-fold plasma clearance (CL/F) and 83% decrease in plasma AUC of apatinib. By contrast, coadministration with itraconazole reduced the CL/F of apatinib by 40% and increased its AUC by 75%. In summary, a strong CYP3A4 inducer (rifampin) had a strong effect (>5-fold) on the clinical pharmacokinetics of apatinib, whereas a strong CYP3A inhibitor (itraconazole 100 mg once a day) had a weak effect (1.25- to 2-fold). Whether these effects are of clinical significance needs further research and information about the exposure-safety and exposure-efficacy relationship of apatinib.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole

Liu

Zhang

Chen

et al. 2017

The Journal of Clinical Pharma

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“…The simulated CL IV and CL oral were 44.0 ± 8.6 and 479.9 ± 356.0 l/h, respectively, which were representative of the calculated observed values of 42 ± 11 and 274.7 ± 94.3 l/h, respectively. The oral clearance in Japanese patients was approximately 44 % (120 ± 54 l/h), of that observed in Caucasian subjects, after a single 20 mg oral dose [6]. .…”

Section: Pbpk Simulationsmentioning

confidence: 83%

A physiologically based pharmacokinetic modeling approach to predict drug–drug interactions between domperidone and inhibitors of CYP3A4

Templeton

Ravenstijn

Sensenhauser

et al. 2016

Biopharm & Drug Disp

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Domperidone is a dopamine receptor antagonist and a substrate of CYP3A4, hence there is a potential for CYP3A inhibition-based drug-drug interactions (DDI). A physiologically based pharmacokinetic model was developed to describe DDIs between domperidone and three different inhibitors of CYP3A4. Simcyp V13.1 was used to simulate human domperidone pharmacokinetics and DDIs. Inputs included domperidone chemical and physical properties (LogP, pKa, etc.), in vitro human liver microsomal data and pharmacokinetic parameters from single-dose intravenous clinical studies in healthy participants. The simulated mean maximum domperidone plasma concentration and AUC after single- and multiple-oral doses under diverse conditions were within 1.1-1.4 fold of the observed values. The simulated intestinal availability, hepatic availability and the fraction absorbed were 0.45 ± 0.14, 0.31 ± 0.10 and 0.89 ± 0.11, respectively, and comparable to observed in vivo values. The simulated ratios of AUC and C(max) in the presence of ketoconazole, erythromycin or itraconazole to baseline were consistent with the observed ratios. Simulated ketoconazole, erythromycin, itraconazole and C(max,ss) and AUC(ss) were within 1.5-fold of the observed values.

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“…Previous works on human subjects as well as animal models suggest that Domperidone goes into a number of drug-drug interactions [10][11][12]. As Ketotifen Fumerarate and Domperidone are often prescribed together, this study investigates the possible interaction between these two drugs through in vitro study.…”

Section: Discussionmentioning

confidence: 99%

A study of in-vitro interaction of Ketotifen Fumarate with Domperidone at different gastric and intestinal pH

Aktar¹,

Mohammed²,

Tareq³

et al. 2014

RusOMJ

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Aim -The main focus of the project was to identify whether there is any interaction between Ketotifen Fumarate (antihistamine) and domperidone (Antiemetic/dopaminergic antagonist) present or not at simulated gastric and intestinal solutions of different pH. Methods -Using Job's continuous-variation analysis the possible drug-drug interaction was determined at a fixed temperature (37ºC) at the studied pH. From Job's continuous-variation analysis the views of drug-drug interaction at different concentration ratio at all pH (0.4, 1.2, 2.0, 2.8, 6.8, and 7.4) except 6.0 were noted. Results -Data obtained from spectroscopic analysis showed decrease in free-drug concentration of both of the drugs analyzed when they were within the same gastric simulated solution. Conclusion -Concurrent administration of Ketotifen Fumarate and domperidone would result in the formation of a stable complex and this is likely to reduce the the rapeutic activities of both drugs.

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Itraconazole and domperidone: a placebo-controlled drug interaction study

Cited by 17 publications

References 33 publications

Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole

Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole

A physiologically based pharmacokinetic modeling approach to predict drug–drug interactions between domperidone and inhibitors of CYP3A4

A study of in-vitro interaction of Ketotifen Fumarate with Domperidone at different gastric and intestinal pH

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